Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance.
Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance.
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DOI：
10.1016/j.atherosclerosis.2012.10.035
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发表时间：
2013-01
期刊：
影响因子：
5.3
通讯作者：
Trischitta V
中科院分区：
文献类型：
--
作者：
Bacci S;Prudente S;Copetti M;Spoto B;Rizza S;Baratta R;Di Pietro N;Morini E;Di Paola R;Testa A;Mallamaci F;Tripepi G;Zhang YY;Mercuri L;Di Silvestre S;Lauro R;Malatino L;Consoli A;Pellegrini F;Pandolfi A;Frittitta L;Zoccali C;Federici M;Doria A;Trischitta V
胰岛素抵抗（IR）和心血管疾病（CVD）有着共同的土壤。我们研究了影响胰岛素信号传导的单核苷酸多态性 (SNP)（ENPP1 K121Q，rs1044498；IRS1 G972R，rs1801278；TRIB3 Q84R，rs2295490）对 CVD、心肌梗死 (MI) 年龄、体内胰岛素敏感性和体外胰岛素刺激一氧化氮合酶 (NOS) 活性的综合作用。 1. 我们首先研究了 733 名患者（2,186 人年，175 起事件）的心血管事件事件（包括心肌梗塞 -MI-、中风和心血管死亡的复合终点）。 2. 在一项复制尝试中，对 331 名个体进行了 MI 年龄测试。 3. 对 829 名空腹血糖 < 126 mg/dl 的个体进行了 OGTT 衍生的胰岛素敏感性指数 (ISI) 评估。 4.测量了40株人静脉内皮细胞(HUVEC)的NOS活性。 1. 风险变异共同预测心血管事件（HR=1.181；p=0.0009），并且当添加到临床风险因素中时，显着改善生存C统计；他们还允许在整个样本（135/733 个人）中进行显着正确的重新分类（通过净重新分类指数），甚至在肥胖患者（116/204 个人）中进行更正确的重新分类。 2. 风险变异与 MI 时的年龄共同相关 (p=0.006)。 3. 还观察到与 ISI 存在显着相关性 (p=0.02)。 4. 最后，风险变异与 HUVEC 中胰岛素刺激的 NOS 活性共同相关（p=0.009）。胰岛素信号基因变异共同影响心血管疾病，很可能是通过促进全身和内皮特异性胰岛素抵抗。需要进一步的研究来解决他们的基因分型是否有助于识别需要特定和/或更积极的预防策略的高危患者。
Insulin resistance (IR) and cardiovascular disease (CVD) share a common soil. We investigated the combined role of single nucleotide polymorphisms (SNPs) affecting insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on CVD, age at myocardial infarction (MI), in vivo insulin sensitivity and in vitro insulin-stimulated nitric oxide synthase (NOS) activity. 1. We first studied, incident cardiovascular events (a composite endpoint comprising myocardial infarction -MI-, stroke and cardiovascular death) in 733 patients (2,186 person-years, 175 events). 2. In a replication attempt, age at MI was tested in 331 individuals. 3. OGTT-derived insulin sensitivity index (ISI) was assessed in 829 individuals with fasting glucose < 126 mg/dl. 4. NOS activity was measured in 40 strains of human vein endothelial cells (HUVECs). 1. Risk variants jointly predicted cardiovascular events (HR=1.181; p=0.0009) and, when added to clinical risk factors, significantly improved survival C-statistics; they also allowed a significantly correct reclassification (by net reclassification index) in the whole sample (135/733 individuals) and, even more, in obese patients (116/204 individuals). 2. Risk variants were jointly associated with age at MI (p=0.006). 3. A significant association was also observed with ISI (p=0.02). 4. Finally, risk variants were jointly associated with insulin-stimulated NOS activity in HUVECs (p=0.009). Insulin signaling genes variants jointly affect cardiovascular disease, very likely by promoting whole body and endothelium-specific insulin resistance. Further studies are needed to address whether their genotyping help identify very high-risk patients who need specific and/or more aggressive preventive strategies.
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DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
168.9
作者：
CLAUSEN, JO;HANSEN, T;PEDERSEN, O
通讯作者：
PEDERSEN, O
影响因子：
8.8
作者：
Berg, Alfred O.;Botkin, Jeffrey;Veenstra, David L.
通讯作者：
Veenstra, David L.
影响因子：
7.7
作者：
Rich, SS;Bowden, DW;Bergmans, RN
通讯作者：
Bergmans, RN
影响因子：
15.9
作者：
Liew, Chong Wee;Bochenski, Jacek;Kulkarni, Rohit N.
通讯作者：
Kulkarni, Rohit N.